PDF: PROMISE-1
(2020)Objective
Eptinezumab 30 mg, 100 mg, and 300 mg intravenously every 12 weeks — to evaluate preventive efficacy and safety in episodic migraine.
Study Summary
• Mean MMD reduction over weeks 1-12: 3.9 (100 mg, p=0.018), 4.3 (300 mg, p=0.0001), 4.0 (30 mg, NS), vs 3.2 (placebo).
• Benefit was apparent from day 1 after the first infusion, reflecting rapid onset with IV administration.
• 30 mg dose did not meet the primary endpoint — showing a dose-response relationship.
• Safety profile favorable, with upper respiratory tract infections and fatigue slightly more frequent than placebo.
• Established eptinezumab as the first IV-administered CGRP pathway antibody (q12-weekly dosing) for migraine prevention.
Intervention
Eptinezumab 30 mg, 100 mg, 300 mg, or placebo IV every 12 weeks for up to 4 doses over 56 weeks.
Inclusion Criteria
Adults 18–75 years with history of episodic migraine (4–14 migraine days/month) per ICHD-3 for ≥12 months.
Study Design
Arms: Placebo vs Eptinezumab 30 mg vs 100 mg vs 300 mg
Patients per Arm: Placebo 222; Eptinezumab 30 mg 223; 100 mg 221; 300 mg 222 (N=888)
Outcome
• Benefit evident on day 1 post-infusion
• ≥50% MMD reduction response rate: higher with 100 mg and 300 mg vs placebo
• AEs: URTI (9.9-11.4% eptinezumab vs 7.2% placebo), fatigue (2.3-3.6% eptinezumab vs <1% placebo)
• No serious hepatotoxicity, anaphylaxis, or cardiovascular signals
Clinical Question
Is IV eptinezumab effective and safe for preventive treatment of episodic migraine?
Bottom Line
Intravenous eptinezumab 100 mg and 300 mg dosed every 12 weeks significantly reduced monthly migraine days vs placebo over weeks 1-12 in adults with episodic migraine, with benefit evident from day 1. The 30 mg dose did not reach the primary endpoint. Established eptinezumab as the first IV CGRP pathway antibody for migraine prevention with a quarterly infusion schedule.
Major Points
- Phase 3 multicenter randomized double-blind placebo-controlled parallel-group trial at 84 sites
- 888 adults with episodic migraine (4-14 MMDs/month) randomized 1:1:1:1
- Four arms: placebo, eptinezumab 30 mg, 100 mg, and 300 mg IV every 12 weeks
- Up to 4 IV doses over 56-week study duration
- Primary endpoint: mean change from baseline in MMD over weeks 1-12
- Mean baseline MMD: 8.6 across arms
- Primary result: MMD reduction weeks 1-12 — 3.2 (placebo), 4.0 (30 mg, NS), 3.9 (100 mg, p=0.018), 4.3 (300 mg, p=0.0001)
- Benefit evident from day 1 after first infusion (rapid onset with IV route)
- ≥50% MMD reduction response rates higher with 100 mg and 300 mg vs placebo
- URTI: 7.2% (placebo), 11.4% (30 mg), 9.9% (100 mg), 10.3% (300 mg)
- Fatigue: <1% (placebo) vs 2.3-3.6% (eptinezumab arms)
- No hepatotoxicity, anaphylaxis, or cardiovascular adverse event signals
- Led to FDA approval of eptinezumab (Vyepti) in 2020 for migraine prevention (episodic and chronic)
- Companion PROMISE-2 trial (chronic migraine) also positive
Study Design
- Study Type
- Phase 3 multicenter randomized double-blind placebo-controlled parallel-group trial
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 888
- Follow-up
- 56 weeks (primary at weeks 1-12)
- Centers
- 84
Primary Outcome
Definition: Mean change from baseline in monthly migraine days (MMD) over weeks 1-12
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| -3.2 (placebo) | -3.9 (100 mg), -4.3 (300 mg), -4.0 (30 mg) | - | 100 mg p=0.018; 300 mg p=0.0001; 30 mg NS |
Limitations & Criticisms
- Placebo response was large (3.2-day reduction), reducing absolute effect size
- 30 mg dose negative — raises questions about minimum effective dose
- No active comparator (subcutaneous CGRP mAb)
- IV administration requires infusion center access — may limit accessibility for some patients
- Long-term (>1 year) safety in migraine population still accruing
- Short 12-week primary window; longer 1-year data reported separately
Citation
Cephalalgia 2020;40(3):241-254